title: Mouse neutrophils express the decoy type 2 interleukin-1 receptor (IL-1R2) constitutively and in acute inflammatory conditions.
abstract: The proinflammatory activities of IL-1 are tightly controlled at different levels. IL-1R2 acts as a decoy receptor and has been shown to regulate the biological effects of IL-1 in vitro and in vivo. However, little is known about its natural expression in the mouse in physiologic and pathologic conditions. In this study, we examined IL-1R2 mRNA and protein expression in isolated cells and tissues in response to different stimulatory conditions. Data obtained using ex vivo CD11b(+)Ly6G(+) peripheral blood cells and in vitro-differentiated CD11b(+)Ly6G(+) BMG indicated that neutrophils are the major source of constitutively expressed IL-1R2 in the mouse. The expression of IL-1R2 on BMG and ex vivo Ly6G(+) peripheral blood cells was highly up-regulated by HC. IL-1R2 pull-down experiments showed that mouse rIL-1β binds to BMG IL-1R2, whereas binding of IL-1Ra could not be detected. Furthermore, LPS treatment induced shedding of IL-1R2 from the neutrophil membrane in vitro and in vivo, executed mainly by ADAM17. Finally, in in vivo models of inflammation, including thioglycolate-induced acute peritonitis and acute lung injury, infiltrating Ly6G(+) neutrophils, expressed IL-1R2. Our data show that in the mouse, neutrophils mainly express the decoy receptor IL-1R2 under naïve and inflammatory conditions. These data suggest that neutrophils may contribute to the resolution of acute inflammation.
authors.affiliation: 1.University Hospitals of Geneva, 26 Avenue Beau-Séjour, 1206 Geneva, Switzerland. cem.gabay@hcuge.ch.
authors.forename: Praxedis
authors.initials: P
authors.lastname: Martin
authors.forename: Gaby
authors.initials: G
authors.lastname: Palmer
authors.forename: Solenne
authors.initials: S
authors.lastname: Vigne
authors.forename: Céline
authors.initials: C
authors.lastname: Lamacchia
authors.forename: Emiliana
authors.initials: E
authors.lastname: Rodriguez
authors.forename: Dominique
authors.initials: D
authors.lastname: Talabot-Ayer
authors.forename: Stefan
authors.initials: S
authors.lastname: Rose-John
authors.forename: Athena
authors.initials: A
authors.lastname: Chalaris
authors.forename: Cem
authors.initials: C
authors.lastname: Gabay
mesh_terms: D000208:Acute Disease; D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006854:Hydrocortisone / Q000494:pharmacology; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology; D053590:Interleukin 1 Receptor Antagonist Protein / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D053574:Receptors, Interleukin-1 Type II / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D053590:Interleukin 1 Receptor Antagonist Protein; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D053574:Receptors, Interleukin-1 Type II; D006854:Hydrocortisone
keywords: LPS; granulocytes; hydrocortisone; shedding